help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on April 24, 2003, doi:10.1165/rcmb.2002-0247OC

Am. J. Respir. Cell Mol. Biol., Volume 29, Number 3, September 2003, 410-418

A more recent version of this article appeared on September 1, 2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2002-0247OCv1
29/3/410    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cobb, B. R
Right arrow Articles by Clancy, J. P
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cobb, B. R
Right arrow Articles by Clancy, J. P

Submitted on November 20, 2002
Revised on April 23, 2003

Adenosine Receptors and Phosphodiesterase Inhibitors Stimulate Cl- Secretion in Calu-3 Cells

Bryan R Cobb1, Lijuan J Fan2, Timea E Kovacs3, Eric J Sorscher4, and John P Clancy2*

1 Department of Human Genetics, University of Alabama at Birmingham, Birmingham, AL, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA, 2 Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA, 3 Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA, 4 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA

* To whom correspondence should be addressed. E-mail: jclancy{at}peds.uab.edu.

We investigated CFTR activation by clinically used phosphodiesterase inhibitors (PDEis) in Calu-3 cell monolayers alone and in combination with A2B adenosine receptor stimulation. This receptor pathway has previously been shown to activate wildtype and mutant CFTR molecules. Several PDEis, including milrinone, cilostazol (Pletal®), papaverine, rolipram, and sildenafil (Viagra®) produced Isc that was glibenclamide sensitive, achieving 20-85% of forskolin-stimulated Isc. Papaverine, cilostazol, and rolipram also augmented both the magnitude and the duration of Isc following low dose stimulation of adenosine receptors with Ado (0.1 to 1.0 µM, p < 0.01). Subsequent studies demonstrated that very low concentrations of cilostazol or papaverine (~1/2 peak serum concentrations) were sufficient to activate Isc, and both agents markedly augmented Ado-stimulated Isc (1 µM, p < 0.01). Our results provide evidence that select PDEis, at concentrations achieved as part of systemic therapies, can activate CFTR-dependent Isc in Calu-3 cell monolayers. These studies also indicate that PDEis have the capacity to augment an endogenous CFTR-activating pathway in an "in vivo"-like model system, and support future investigations of these agents relevant to cystic fibrosis.




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
B. M. Rollins, M. Burn, R. D. Coakley, L. A. Chambers, A. J. Hirsh, M. T. Clunes, M. I. Lethem, S. H. Donaldson, and R. Tarran
A2B Adenosine Receptors Regulate the Mucus Clearance Component of the Lung's Innate Defense System
Am. J. Respir. Cell Mol. Biol., August 1, 2008; 39(2): 190 - 197.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
D. Wang, Y. Sun, W. Zhang, and P. Huang
Apical adenosine regulates basolateral Ca2+-activated potassium channels in human airway Calu-3 epithelial cells
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1443 - C1453.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Sun, F. Wu, F. Sun, and P. Huang
Adenosine Promotes IL-6 Release in Airway Epithelia
J. Immunol., March 15, 2008; 180(6): 4173 - 4181.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
L. L. Clarke
Phosphodiesterase 5 Inhibitors and Cystic Fibrosis: Correcting Chloride Channel Dysfunction
Am. J. Respir. Crit. Care Med., March 1, 2008; 177(5): 469 - 470.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. Lubamba, H. Lecourt, J. Lebacq, P. Lebecque, H. De Jonge, P. Wallemacq, and T. Leal
Preclinical Evidence that Sildenafil and Vardenafil Activate Chloride Transport in Cystic Fibrosis
Am. J. Respir. Crit. Care Med., March 1, 2008; 177(5): 506 - 515.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
A Moeller, F Horak Jr, C Lane, D Knight, A Kicic, S Brennan, P Franklin, J Terpolilli, J H Wildhaber, and S M Stick
Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis
Thorax, June 1, 2006; 61(6): 514 - 520.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
Y. Li, W. Wang, W. Parker, and J. P. Clancy
Adenosine Regulation of Cystic Fibrosis Transmembrane Conductance Regulator through Prostenoids in Airway Epithelia
Am. J. Respir. Cell Mol. Biol., May 1, 2006; 34(5): 600 - 608.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
M. L. Palmer, S. Y. Lee, P. J. Maniak, D. Carlson, S. C. Fahrenkrug, and S. M. O'Grady
Protease-activated receptor regulation of Cl- secretion in Calu-3 cells requires prostaglandin release and CFTR activation
Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1189 - C1198.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
Z. Bebok, J. F. Collawn, J. Wakefield, W. Parker, Y. Li, K. Varga, E. J. Sorscher, and J. P. Clancy
Failure of cAMP agonists to activate rescued {Delta}F508 CFTR in CFBE41o- airway epithelial monolayers
J. Physiol., December 1, 2005; 569(2): 601 - 615.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Liu, A. Veilleux, L. Zhang, A. Young, E. Kwok, F. Laliberte, C. Chung, M. R. Tota, D. Dube, R. W. Friesen, et al.
Dynamic Activation of Cystic Fibrosis Transmembrane Conductance Regulator by Type 3 and Type 4D Phosphodiesterase Inhibitors
J. Pharmacol. Exp. Ther., August 1, 2005; 314(2): 846 - 854.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. P. Barnes, G. Livera, P. Huang, C. Sun, W. K. O'Neal, M. Conti, M. J. Stutts, and S. L. Milgram
Phosphodiesterase 4D Forms a cAMP Diffusion Barrier at the Apical Membrane of the Airway Epithelium
J. Biol. Chem., March 4, 2005; 280(9): 7997 - 8003.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. R. Lazarowski, R. Tarran, B. R. Grubb, C. A. van Heusden, S. Okada, and R. C. Boucher
Nucleotide Release Provides a Mechanism for Airway Surface Liquid Homeostasis
J. Biol. Chem., August 27, 2004; 279(35): 36855 - 36864.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. Hentchel-Franks, D. Lozano, V. Eubanks-Tarn, B. Cobb, L. Fan, R. Oster, E. Sorscher, and J. P. Clancy
Activation of Airway Cl- Secretion in Human Subjects by Adenosine
Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 140 - 146.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S.-N. Wu, S.-I. Liu, and M.-H. Huang
Cilostazol, an Inhibitor of Type 3 Phosphodiesterase, Stimulates Large-Conductance, Calcium-Activated Potassium Channels in Pituitary GH3 Cells and Pheochromocytoma PC12 Cells
Endocrinology, March 1, 2004; 145(3): 1175 - 1184.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
R. E. Bucheimer and J. Linden
Purinergic regulation of epithelial transport
J. Physiol., March 1, 2004; 555(2): 311 - 321.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2003 American Thoracic Society. 		  2009 ATS Conference